HEMATOLOGY/ONCOLOGY SUMMARY

A companion to PowerPoint IVMS Hematology-Blood Physiology and Pathology Overview | Review

Terms Platelet

Macrophage

Eosinophils

Basophils

Mast cell

Factor XII

Definitions - contains dense granules (ADP, calcium) and -granules (vWF, fibrinogen) - approximately 1/3 of the body's platelet pool is stored in spleen - life span of 8-10 days - vWF receptor: GpIb - Fibrinogen receptor: GpIIb/IIIb - Phagocytoses bacteria, cell debris, and senescent red cells and scavenges damaged cells and tissues - long life in tissues - activated by -interferon - can function as APC via MHC II - CD14 surface marker - bilobate nucleus - packed with large eosinophilic granules of uniform size - highly phagocytic for Ag-Ab complexes - produces histamine and arylsulfatase (help limit reaction following mast cell degranulation) - causes of eosinophilia: neoplasia, asthma, allergic processes, collagen vascular diseases, parasites - mediates allergic reactions - bilobated nucleus - densely basophilic granules contain: heparin (anticoagulant), histamine (vasodilator), and other vasoactive amines, and leukotrienes (LTD4) - found in blood - mediates allergic reaction - degranulation - histamine, heparin, and eosinophil chemotatic factors - can bind the Fc portion of IgE to membrane - structurally and functionally similar to basophils - involved in type I hypersensitivity reactions - found in tissue - first step of the intrinsic pathway - activated by collagen, basement membrane, activated platelets, and HMWK (bradykinin precursor) - activates factor XI and converts prokallikrein to kallikrein
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Hematology-Oncology Summary /mic-12-13

Kallikrein

Bradykinin

Common coagulation pathway Factors effected by Vitamin K deficiency

Antithrombin

Protein C

tPA platelet plug formation

Aggregation balance

- activated by factor XII - converts HMWK to bradykinin (kinin cascade) - converts plasminogen to plasmin (degrades fibrin) - part of Kinin cascade, activated by intrinsic coagulation pathway - vasodilation - permeability - pain - X (+V) II (aka thrombin) Fibrin aggregation (by XIII and Ca2+) - both extrinsic and intrinsic pathways convert on factor X Factor II (thrombin, common pathway) Factor VII (extrinsic pathway) Factor IX (intrinsic pathway) Factor X (common pathway protein C protein S - vit K activated by epoxide reducatase cofactor in maturation of II, VII, IX, X, C, and S from precusors - activated by heparin - inhibits thrombin and: factor VII (extrinsic) factor IX (intrinsic) factor X (common) factor XI (intrinsic) factor XII (intrinsic) - Protein C is activated by thrombomodulin from endothelial cells - protein S assist activated protein C in the cleavage and inactivation of Va and VIIIa - activates plasmin, which degrades fibrin - used as a thrombolytic - injury: vWF binds to exposed collagen - adhesion: platelets bind vWF via GpIb receptor and release ADP and Ca2+ (necessary for coagulation cascade) - ADP: helps platelets adhere to endothelium, ADP binding to receptor induces GpIIb/IIIa expression at platelet surface aggregation: fibrinogen binds GpIIb/IIIa receptors and links platelets - Pro-aggregation factors: TXA2 (released by platelets) blood flow and platelet aggregation
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Hematology-Oncology Summary /mic-12-13

Drugs that disrupt thrombogenesis

Erythrocyte sedimentation rate

Pathologic RBC forms: acanthocyte Pathologic RBC forms: basophilic stippling

Pathologic RBC forms: Elliptocyte Pathologic RBC forms: macro-ovalocyte Pathologic RBC forms: ringed sideroblasts Pathologic RBC forms: schistocyte Pathologic RBC forms: spherocyte Pathologic RBC forms: teardrop cell Pathologic RBC forms: target cells

- Anti-aggregation factors: PGI2 and NO (released by endothelial cells) blood flow and platelet aggregation - aspirin: cyclooxygenase ( TXA2 synthesis) - Ticlopidine and clopidogrel: inhibits ADP-induced expression of GpIIb/IIIa (platelets can't cross link) - Abciximab: inhibits GpIIb/IIIa directly - acute-phase reactants in plasma can cause RBC aggregation, thereby RBC sedimentation rate - ESR: infections, inflammatory diseases, malignany neoplasms, GI disease, pregnancy - ESR: polycythemia, sickle cell anemia, CHF, microcytosis, hypofibrinogenemia (AKA: spur cell) - liver disease - abetalipoproteinemia - Thalassemia - Anemia of chronic disease - Iron deficiency - Lead poisoning - hereditary elliptocytosis - megaloblastic anemia (also hypersegmented PMNs) - marrow failure - sideroblastic anemia - DIC - TTP/HUS - traumatic hemolysis - hereditary spherocytosis - autoimmune hemolysis - bone marrow infiltration - HbC disease - Asplenia - Liver disease - Thalassemia - oxidation of iron from ferrous to ferric form leads to **denatured hemoglobin precipitation and damage to RBC membrane - -thalassemia - G6PD deficiency
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Pathologic RBC forms: Heinz bodies

Hematology-Oncology Summary /mic-12-13

Pathologic RBC forms: Howell-Jolly bodies Microcytic anemias

Normocytic, nonhemolytic anemias Hemolytic anemias intrinsic

Hemolytic anemias extrinsic

Megaloblastic anemias Macrocytic, nonmegaloblastic anemias

Iron deficiency anemia

-thalassemia

- basophilic nuclear remnants found in RBCs - due to functional hyposplenia or asplenia - Iron deficiency - Anemia of chronic disease (may initially present as normocytic anemia) - Thalassemias - Lead poisoning - Sideroblastic anemia - Anemia of chronic disease (progresses to microcytic) - Aplastic anemia - Kidney disease - RBC membrane defect: hereditary spherocytosis - RBC enzyme deficiency: G6PD, pyruvate kinase deficiency - HcC - Sickle cell anemia - Paroxysmal nocturnal hemoglobinuria - Autoimmune - Microangiopathic hemolytic anemia (MIHA) - Macroangiopathic hemolytic anemia (MAHA) - Infections - Folate deficiency - B12 deficiency - DNA synthesis is impaired -caused by liver disease, alcoholism, reticulocytosis MCV, metabolic disorders, congenital deficiencies of purine and pyrimidine synthesis and drugs (5-FU, zidovudine, hydroxyurea) - microcytic, hypochromic - iron heme synthesis - Plummer-Vinson: iron deficiency anemia, esophageal web, atrophic glossitis - Labs: serum iron transferrin or TIBC ferritin % transferrin saturation - microcytic, hypochromic - defect in -globin gene mutation -globin synthesis - prevalent in Asian and African populations - peripheral blood smear: basophilic stippling, target cells, Heinz bodies - 4 gene deletion = hydrops fetalis, (Hb Barts, 4)
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Hematology-Oncology Summary /mic-12-13

-thalassemia minor

-thalassemia major

HbS/-thalassemia heterozygotes Lead poisoning anemia

Sideroblastic anemia

- 3 gene deletion = HbH disease (4) - 1-2 gene deletion = no significant anemia - microcytic, hypochromic - point mutations in splice sites and promoter sequences globin synthesis - HbF (22) - peripheral smear: anisocytosis, poikilocytosis, target cells, schistocytes - seen in Mediterranean populations - minor = heterozygote - chain is underproduced - usually asymptomatic - Diagnosis confirmed by HbA2 (22) on electrophoresis - microcytic, hypochromic - point mutations in splice sites and promoter sequences globin synthesis - HbF (22) - seen in Mediterranean populations - major = homozygote - chain is absent severe anemia requiring blood transfusions - presents with marrow expansion skeletal deformities, Chipmunk facies - mild to moderat sickle cell disease depending on amount of globin production - microcytic, hypochromic - lead inhibits ferrochelatase and ALA dehydratase heme synthesis, protoporphyrin in blood - also inhibits rRNA degredation - presents with lead lining the epiphyses of long bones on x-ray, encephalopathy, erythrocyte basophilic stippling, abdominal colic, wrist/foot drop and sideroblastic anemia - adults: headache, memory loss, demyelination - treatment: Dimercaprol, EDTA, and succimer (for kids) - microcytic, hypochromic - defect in heme synthesis - Hereditary: x-linked defect in -aminolevulinic acid synthase gene - reversible etiologies: alcohol, lead - peripheral smear: ringed sideroblasts (from iron-laden mitochondria) - Labs: iron, normal TIBC, ferritin
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Hematology-Oncology Summary /mic-12-13

Folate Deficiency Megaloblastic anemia

B12 deficiency megaloblastic anemia

Intravascular hemolysis

Extravascular hemolysis

Anemia of Chronic Disease

aplastic anemia

Hereditary spherocytosis

- treatment: pyridoxine (B6) therapy - macrocytic - impaired DNA synthesis maturation of nucleus delayed - ineffective erythropoiesis pancytopenia - presents with hypersegmented neutrophils, glossitis, folate, homocyseine but normal methylmalonic acid - macrocytic - impaired DNA synthesis maturation of nucleus delayed - ineffective erythropoiesis pancytopenia - causes: insufficient intake, malabsorption, pernicious anemia, Diphyllobothrium latum (fish tapeworm) - presents with hypersegmented neutrophils, glossitis, B12, homocysteine, methylmalonic acid - Neurological symptoms: due to B12 involvement in fatty acid pathway peripheral neuropathy (sensorimotor), posterior column (vib/proprio), spasticity, dementia - haptoglobin (cleans up spilled heme, decrease means it is being used) - Lactate dehydrogenase - hemoglobin in urine - macrophages in spleen clears RBCs - LDH - unconjugated bilirubin jaundice - nonhemolytic, normocytic anemia - chronic inflammation hepcidin release of iron from macrophages - hepcidin - released by liver, binds ferroportin on intestinal mucosal cells and macrophages thus inhibiting iron transport - labs: iron, TIBC, ferritin - can become microcytic, hypochromic in long standing disease - nonhemolytic, normocytic anemia - failure or destruction of myeloid stem cells (radiation, drugs, viral, Fanconi's anemia, idiopathic) - pancytopenia, normal cell morphology but with hypocellular bone marrow (fatty infiltration) - presents with: fatigue, malaise, pallor, purpura, mucosal bleeding petechiae, infection - treatment: withdrawal cause, allogeneic marrow transplant, transfusion, granulocyte colony stimulating factor (G-CSF), GMCSF - intrinsic hemolytic, normocytic anemia
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Hematology-Oncology Summary /mic-12-13

Mean Cell Volume (MCV)

Mean cell hemoglobin concentration (MCHC)

Red cell distribution width (RDW)

G6PD deficiency

Pyruvate kinase deficiency

HbC defect

- extravascular hemolysis - defects in ankyrin, band 3, protein 4.2, or spectrin which are involved in cytoskeleton and membrane integrity - less membrane spherocytes premature removal by spleen - labs: MCHC, RDW - presents with splenomegaly, aplastic crisis (B19 infections), positive osmotic fragility test - treat with splenectomy - Average **size of red blood cells - Normal range: 80-100 fL (1 fL = 10-15 L) - Differentiates between microcytic (MCV < 80) normocytic (MCV 80-100) macrocytic (MCV >100) anemias - Concentration of Hgb RBC - expresses coloration** - Normal range: 32-36 g/dL - Differentiates between hypochromic (MCHC < 32) and normochromic (MCHC 32-36) anemias - normochromic cells have a "zone of central pallor" (that white dot in the middle of the cell) that is no more than 1/3 the diameter of the red cell. - Hypochromic red cells have just a thin rim of hemoglobin. - Standard deviation of the MCV - Tells you how much the RBC differ from each other in size. Anisocytosis - If they are all pretty similar in size, the RDW is low. - If some are little and some are big, the RDW is high. - Normal range = 12-13.5% - intrinsic hemolytic, normocytic anemia - intravascular and extravascular hemolysis - x-linked - hemolytic anemia follows oxidative stress - presents with back pain and hemoglobinuria a few days later - intrinsic hemolytic, normocytic anemia - extravascular hemolysis - autosomal recessive - defect in pyruvate kinase ATP rigid RBCs pyruvate kinase catalyzes pyruvate to lactate - hemolytic anemia in newborns - intrinsic hemolytic, normocytic anemia - glutamic acid-to-lysine mutation at position 6 in chain mutation
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Hematology-Oncology Summary /mic-12-13

Paroxysmal nocturnal hemoglobinuria

Sickle cell anemia

autoimmune hemolytic anemia

Erythroblastosis fetalis

Direct Coomb's test Indirect Coomb's test Microangiopathic anemia

Macroangiopathic anemia

Hemochromatosis

- patients with HbSC (1 of each mutated gene) have milder disease than do HbSS patients - intrinsic hemolytic, normocytic anemia - intravascular hemolysis - complement-mediated RBC lysis - impaired synthesis of GPI anchor/decay-accelerating factor in RBC membrane - urine hemosiderin - complication: thrombosis - point mutation on -chain (glutamic acid valine at position 6) - sickling from low O2 or dehydration - complications: aplastic crisis (Parvovirus B19), autosplenectomy, splenic sequestration crisis, salmonella osteomyelitis, painful crisis (dactylitis [painful hand swelling], acute chest syndrome), renal papillary necrosis, microhematuria - treatment: hydroxuria (HbF), bone marrow transplant - extrinsic hemolytic, normocytic anemia - warm agglutination (IgG) - chronic anemia seen in SLE, CLL, or with certain drugs - cold agglutination (IgM) - acute anemia triggered by cold, seen in CLL, Mycoplasma pneumonia infections, or mononucleosis - usually Coomb's test positive - seen in newborns due to Rh or other blood antigen incompatibility - mother's Ab attack fetal RBCs - anti-Ig antibody added to patient's RBCs agglutinate if RBCs are coated with Ig - normal RBCs added to a patient's serum agglutinate if serum has anti-RBC surface Ig - extrinsic hemolytic, normocytic anemia - intravascular hemolysis - RBCs are damaged when passing through obstructed or narrow vessel lumina - seen in DIC, TTP-HUS, SLE, and malignant hypertension - schistocytes on blood smear - extrinsic hemolytic, normocytic anemia - intravascular hemolysis - prosthetic heart valves and aortic stenosis may also cause hemolytic anemia, mechanical destruction - schistocyte on peripheral smear - labs:
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Hematology-Oncology Summary /mic-12-13

Acute intermittent porphyria

Porphyria cutanea tarda

PT (prothrombin time)

aPTT (Partial Thromboplastin Time) Hemophilia

Platelet disorders

Bernard-Soulier disease

Glanzmann's thrombasthenia

serum iron transferrin ferritin % transferrin saturation - defective heme synthesis that leads to accumulation of heme precursors - affected enzyme: porphobilinogen deaminase - accumulation of porphobilinogen, - ALA, uroporphyrin - presents with painful abdomen, red wine colored urine, polyneuropathy, psychological disturbance, precipitated by drugs - treat with glucose and heme - defective heme synthesis that leads to accumulation of heme precursors - affected enzyme: Uroporphyrinogen decarboxylase - accumulation of uroporphyrin - blistering cutaneous photosensitivity - most common porphyria - tests the extrinsic pathway - factor VII (also I, II, V, and X) - defect leads to increased time - tests the intrinsic pathway - all factors except VII and XIII - defect leads to increased time - aPTT - A: deficiency in VIII - B: deficiency in IX - macrohemorrhage, hemarthroses, easy bruising - defect in platelet plug formation bleeding time - platelet abnormalities microhemorrhages, mucous membrane bleeding, epitaxis, petechiae, purpura, bleeding time, possible platelet count - Bernard-Soulier disease, Glanzmann's thrombathenia, idiopathic thrombocytopenic purpura (ITP), Thrombotic thrombocytopenic purpura (TTP) - defect in platelet plug formation - GpIb defect in platelet to collagen adhesion - platelet count - Bleeding time - defect in platelet plug formation - GpIIb/IIIa defect in platelet to platelet aggregation - bleeding time, blood smear shows no platelet clumping
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Hematology-Oncology Summary /mic-12-13

Idiopathic thrombocytopenic purpura (ITP)

Thrombotic thrombocytopenic purpura (TTP)

von Willebrand's disease

DIC

Factor V Leiden

Prothrombin gene mutation Antithrombin deficiency

Protein C or S deficiency

Blood transfusion therapy: packed RBCs Blood transfusion therapy: platelets

- platelet survival - anti- GpIIb/IIIa antibodies peripheral platelet destruction - megakaryocytes - bleeding time - platelet count - platelet survival - deficiency of ADAMTS 13 degradation of vWF multimers platelet aggregation and thrombosis - Labs: schistocytes, LDH - presents with pentad of neurologic and renal symptoms, fever, thrombocytopenia, and microangiopathic hemolytic anemia - platelet count - bleeding time - vWF carries and protects factor VIII, connects GpIb of platelet to collagen - defect of intrinsic pathway, vWF may see aPTT - defect of platelet adhesion to collagen bleeding time - mild, but most common bleeding disorder - treatment: desmopressin (releases vWF stored in epithelial cells) - wide spread activation of clotting leads to a deficiency in clotting factors bleeding state - caused by sepsis (G (-)), trauma, obstetric complications, acute pancreatitis, Malignancy, Nephrotic syndrome, Transfusion - Labs: schistocytes, fibrin split product (D-dimer), fibrinogen, factors V and VII - production of mutant factor V that cannot be degraded by protein C - most common cause of inherited hyprcoagulability - leads to hypercoagulable state - mutation in 3' untranslated region associated with venous clots - leads to hypercoagulable state - inherited deficiency of antithrombin - reduced in PTT after administration of heparin - leads to hypercoagulable state - ability to inactivate factors V and VIII - risk of thrombotic skin necrosis with hemorrhage following administration of warfarin - Hb and O2 carrying capacity - acute blood loss and severe anemia - platelet count - usually given in 6 platelet units for therapeutic effect
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Hematology-Oncology Summary /mic-12-13

Blood transfusion therapy: Fresh frozen plasma Blood transfusion therapy: cryoprecipitate Blood transfusion risks

Hodgkin's lymphoma

Non-Hodgkin's lymphoma

Nodular sclerosing Hodgkin's lymphoma

Mixed cellularity Hodgkin's lymphoma

Lymphocyte predominant

- stop significant bleeding (thrombocytopenia, qualitative platelet defects) - coagulation factor levels by about 20% - treats DIC, cirrhosis, warfarin over-anticoagulation - contains fibrinogen, factor VIII, factor XIII - treats coagulation factor deficiencies involving fibrinogen and factor VIII - infection - reactions - iron overload - hypocalcemia - citrate is a calcium chelator - hyperkalemia - RBCs may lyse in older blood units - Reed-Sternberg cells (CD30+/CD15+) - localized to single group of nodes - contiguous spread - constitutional signs/symptoms - low-grade fever, night sweats, weight loss - mediastinal lymphadenopathy - 50% of cases associated with EBV - bimodal age distribution - more common in men except the nodular sclerosing type (lacunar variant of RS cells) - good prognosis = lymphocytes, RS cells - may be associated with HIV and immunosuppression - multiple peripheral nodes - extranodal involvement common - noncontiguous spread - majority involve B cells (except for those of lymphoblastic T cell origin) - fewer constitutional signs/symptoms - peak incidence for certain subtypes at 20-40 years - most common type (65-75%) - variant type RS cells - increased # of lymphocytes - excellent prognosis - collagen banding, women >men, primarily young adults - lots of RS cells - increased lymphocytes - intermediate prognosis - 25% of Hodgkin's lymphoma cases - seen in males under 35
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Hematology-Oncology Summary /mic-12-13

Hodgkin's lymphoma

Lymphocyte depleted Hodgkin's lymphoma

Burkitt's lymphoma

Diffuse large B-cell lymphoma

Mantle cell lymphoma

Follicular lymphoma

Adult T cell lymphoma

Mycosis fungoides/Sezary syndrome

Multiple myeloma

- some RS cells, lymphocytes - excellent prognosis - 6% of Hodgkin's lymphoma cases - slight increase in lymphocytes - RS high relative to lymphocytes - seen in older males with disseminated disease - poor prognosis - non-Hodgkin's lymphoma - seen in young adults - genetics: t(8;14) c-myc gene moves next to heavy-chain Ig gene - "starry-sky" appearance - sheets of lymphocytes with interspersed macrophages - EBV - Jaw lesion most common, pelvis or abdomen in sporadic form - non-Hodgkin's lymphoma - usually seen in older adults, 20% in kids - most common NHL - may be of mature T cell origin (20%) - non-Hodgkin's lymphoma, B cell - seen in older males - genetics: t(11;14) overexpression of cyclin D regulatory gene - CD5+ - poor prognosis - non-Hodgkin's lymphoma, B cell - seen in adults - genetics: t(14;18) bcl-2 expression inhibits apoptosis - difficult to cure, indolent course - non-Hodgkin's lymphoma, T cell - seen in adults - caused by HTLV-1 - adults present with cutaneous lesions - especially effects populations in Japan, West Africa, and the Caribbean - aggressive - non-Hodgkin's lymphoma, T cell - seen in adults - adults present with cutaneous patches/nodules - indolent CD4+ - monoclonal plasma cell (fried egg appearance) cancer that arises from the marrow and produces large amounts of IgG (55%) or IgA (25%)
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Hematology-Oncology Summary /mic-12-13

MGUS

Leukemias

ALL - Acute lymphoblastic leukemia/lymphoma

SLL - small lymphocytic lymphoma/CLL - chronic lymphocytic leukemia

Hairy cell leukemia

AML - Acute myelogenous leukemia

- most common 1 tumor arising within bone in the elderly - intracytoplasmic inclusions containing Ig - CRAB: hyperCalcemia Renal insufficiency Anemia Bone lytic lesions Back pain (distinguish from Waldenstrom's macroglobulinemia M spike = IgM, and no lytic bone lesions) - monoclonal gammopathy of undetermined significance - monoclonal plasma cell expansion without symptoms of multiple myeloma - unregulated growth of leukocytes in bone marrow - or number of circulating leukocytes in blood and marrow failure - anemia, infections, & hemorrhage - leukemic cell infiltrates in liver, spleen, and lymph nodes are possible - usually seen < 15 y/o - may present with BM involvement in children or mediastinal mass in adolescent males - BM replaced by lymphoblasts - TdT+ (marker of pre-T/B cells) - CALLA+ - most responsive to therapy - may spread to CNS or testes - genetics: t(12;21) - usually seen > 60 y/o - often asymptomatic - smudge cells in peripheral smear - warm antibody autoimmune hemolytic anemia - SLL is same as CLL except CLL has peripheral blood lymphocytes - seen in adults - Mature B cell tumor in elderly - cells have filamentous hairlike projections - stain TRAP (tartrate-resistant acid phosphatase) positive - seen in 60 y/o - Histo: Auer rods in cytoplasm - circulating myeloblasts on peripheral smear - genetics: t(15;17) M3 AML (acute promyelocytic leukemia)
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Hematology-Oncology Summary /mic-12-13

CML - Chronic myelogenous leukemia

Auer bodies

Langerhans cell histiocytosis (LCH)

Polycythemia vera

Essential thrombocytosis

Myelofibrosis

responds to all-trans retinoic acid (vitamin A), which induces differentiation of myeloblasts - DIC is common presentation - 30-60 y/o - Philadelphia chromosome - t(9;22), bcr-abl - JAK2 mutation? - myeloid stem cell proliferation - presents with RBC, neutrophils, metamyelocytes, basophils, platelets; splenomegaly - may accelerate and transform to AML or ALL (blast crisis) - very low leukocyte alkaline phosphatase due to immature granulocytes - treat with imatinib - peroxidase-positive cytoplasmic inclusions in granulocytes and myeloblasts - commonly seen in acute promyelocytic leukemia (M3) - treatment of AML M3 can release Auer rods DIC - proliferative disorder of dendritic (langerhans) cells from monocyte lineage - etiology unknown - cells are functionally immature and do not efficiently stimulate T lymphocytes - cells express S-100 and CD1a - Birbeck granules (look like tennis rackets on EM) - chronic myeloproliferative disorders - abnormal clone of hematopoietic stem cells are increasingly sensitive to growth factor - RBCs ( plasma volume, RBC mass) - WBCs - platelets - genetics: JAK2+ - chronic myeloproliferative disorders - similar to polycythemia vera, but specific for megakaryocytes - platelets - genetics: JAK2+ (30-50%) - chronic myeloproliferative disorders - fibrotic obliteration of BM - teardrop cells in blood smear - RBCs - variable amounts of WBCs - variable amounts of platelets
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Hematology-Oncology Summary /mic-12-13

Drug: Cytarabine

Drug: Dactinomycin/ Actinomycin

Drug: Busulfan

Drug: Tacrolimus

Drug: Azathioprine

Muromonab

Pernicious anemia

- neoplastic drug, antimetabolite - pyrimidine analog inhibition of DNA polymerase - S-phase specific - treats: AML, ALL, high-grade non-Hodgkin's lymphoma - toxicity: leukopenia, thrombocytopenia, megaloblastic anemia - antitumor antibiotics - intercalates in DNA - treats: Wilms' tumor, Ewing's sarcoma, rhabdomyosarcoma - used for childhood tumors - toxicity: myelosuppression - alkylating agent - alkylates DNA - Treats: CML - also used to ablate patient's bone marrow before bone marrow transplant - toxicity: pulmonary fibrosis, hyperpigmentation - binds to FK-binding protein, inhibiting secretion of IL-2 and other cytokines - similar to cyclosporine - potent immunosuppressant used in organ transplant - Toxicity: nephrotoxicity, peripheral neuropathy, hypertension, pleural effusion, hyperglycemia - antimetabolite precursor of 6-mercaptopurine that interferes with the metabolism and synthesis of nucleic acids - toxic to proliferating lymphocytes - used for kidney transplantation and autoimmune disorders (glomerulonephritis and hemolytic anemia) - Toxicity: BM suppression - Active metabolite mercaptopurine is metabolized by xanthine oxidase, toxic effects by allopurinol - AKA: OKT3 - monoclonal antibody that binds CD3 on the surface of T cells - blocks cellular interaction with CD3 protein responsible for T cell signal transduction - used for immunosuppression after kidney transplant - Toxicity: cytokine release syndrome, hypersensitivity reaction - type II hypersensitivity reaction - autoantibodies against proton pump in parietal cells (85-90%), antibodies that block binding of vitamin B12 to intrinsic factor (60-75%), antibodies that prevent binding of B12-IF complexes to ileal receptors (30-50%)
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Hematology-Oncology Summary /mic-12-13

- presents with achlorhydria (lack of gastric acid) due to parietal cell destruction, chronic gastritis, increased risk of gastric carcinoma, elevated serum gastrin, and signs of vitamin B12 deficiency

Hematology-Oncology Summary /mic-12-13

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